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Abstract

Development of Novel Crystal Forms of Metaxalone for Solubility Enhancement

Author(s): M. S. AZIZ, CHITRA GUPTA AND L. K. TYAGI*
Lloyd Institute of Management and Technology (Pharm.), Plot No.11, Knowledge Park-II, Greater Noida, Uttar Pradesh 201306, India

Correspondence Address:
L. K. TYAGI, Lloyd Institute of Management and Technology (Pharm.), Plot No.11, Knowledge Park-II, Greater Noida, Uttar Pradesh 201306, India, Email: [email protected]


Metaxalone is oxazolidin-2-one derivative, biopharmaceutics classification system class II drug, available in the market as a central muscle relaxant drug, used to alleviate discomforts associated with severe, painful musculoskeletal conditions. The major drawbacks associated with formulation of solid oral dosage forms of metaxalone are its poor aqueous solubility, poor flow property and low compressibility. The aim of present study was to develop different crystalline forms of metaxalone in order to overcome these drawbacks and consequently enhance its dissolution and bioavailability. For this purpose two different approaches were adopted namely cocrystallization and melt sonocrystallization. Cocrystals of metaxalonesaccharin and metaxalone-lactic acid were prepared, with saccharin and lactic acid as coformers, by using solvent evaporation method. Melt sonocrystallization technique was applied for preparation of melt sonocrystallized form of metaxalone. The percentage yield, melting point, particle size, flow property, crystallinity index, solubility and dissolution profiles of developed crystals were evaluated and compared with original metaxalone. Further the developed forms of metaxalone were characterized by differential scanning calorimetry, fourier transform infrared spectroscopy, X-ray diffraction and scanning electron microscopy. The sharp peak of differential scanning calorimetry thermograms and fourier transform infrared spectroscopy spectras indicate towards the formation of crystalline forms with retention of characterstic functionality of original metaxalone. The particle size and crystallinity index of the developed metaxalone crystals were significantly reduced in comparison to the original form. In addition, there was significant enhancement in the flow and compressibility of developed crystals, as indicated by the value of angle of repose, Carr’s index and Hausner ratio. The solubility of prepared crystals was much higher as compared to metaxalone and progressively increased in the following order: metaxalonesaccharin< metaxalone-lactic acid<melt sonocrystallized form of metaxalone. The dissolution studies revealed that 87.08, 92.79 and 99.79 % of the drug was released within 30 min from metaxalone-saccharin, metaxalone-lactic acid and melt sonocrystallized form of metaxalone crystals, respectively compared to 67.63 % release from the original metaxalone drug. Further maximum solubility and faster dissolution was observed with melt sonocrystallized form of metaxalone as compared to metaxalone-lactic acid and metaxalone-saccharin. On the basis of this it can be concluded that solvent evaporation method and melt sonocrystallization techniques are promising techniques that may afford crystals with improved flow property, improved solubility and dissolution.

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